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Most Popular Herbicide Glyphosate Causes Autism Stephanie Seneff MIT CSAIL April 28, 2014 GLYPHOSATE

Most Popular Herbicide Glyphosate Causes Autism Stephanie Seneff MIT CSAIL April 28, 2014 GLYPHOSATE

A Frightening Trend* *K. Weintraub, Nature 479, Nov. 3 2011, 22 -24. ? ?

A Frightening Trend* *K. Weintraub, Nature 479, Nov. 3 2011, 22 -24. ? ?

“If it is an environmental cause contributing to an increase, we certainly want to

“If it is an environmental cause contributing to an increase, we certainly want to find it. ”* *K. Weintraub, Nature 479, Nov. 3 2011, 22 -24.

“Autism is a multi-factorial condition”

“Autism is a multi-factorial condition”

“Autism is a single-factorial condition”

“Autism is a single-factorial condition”

GLYPHOSATE

GLYPHOSATE

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Glyphosate and Autism* R = 0. 9898; p <= 2. 6 e-06 Pearson Correlation

Glyphosate and Autism* R = 0. 9898; p <= 2. 6 e-06 Pearson Correlation Coefficient = 0. 99 *Nancy Swanson, http: //www. examiner. com/article/ data-show-correlations-between-increase-neurological-diseases-and-gmos

Glyphosate and Autism* U. S. Market is 25% of World Market of Roundup R

Glyphosate and Autism* U. S. Market is 25% of World Market of Roundup R = 0. 9898; p <= 2. 6 e-06 Pearson Correlation Coefficient = 0. 99 *Nancy Swanson, http: //www. examiner. com/article/ data-show-correlations-between-increase-neurological-diseases-and-gmos

Is Glyphosate Nontoxic? • Monsanto has argued that glyphosate is harmless to humans because

Is Glyphosate Nontoxic? • Monsanto has argued that glyphosate is harmless to humans because our cells don’t have the shikimate pathway, which it inhibits • However, our gut bacteria DO have this pathway – We depend upon them to supply us with essential amino acids (among many other things) • Other ingredients in Roundup greatly increase glyphosate’s toxic effects • Insidious effects of glyphosate accumulate over time – Most studies are too short to detect damage

Main Toxic Effects of Glyphosate* • Kills beneficial gut bacteria and allows pathogens to

Main Toxic Effects of Glyphosate* • Kills beneficial gut bacteria and allows pathogens to overgrow • Interferes with function of cytochrome P 450 (CYP) enzymes • Chelates important minerals (iron, cobalt, manganese, etc. ) • Interferes with synthesis of aromatic amino acids and methionine – Leads to shortages in critical neurotransmitters and folate • Disrupts sulfate synthesis and sulfate transport *Samsel and Seneff, Entropy 2013, 15, 1416 -1463

The Enhancing Effect of Adjuvants* “Adjuvants in pesticides are generally declared as inerts, and

The Enhancing Effect of Adjuvants* “Adjuvants in pesticides are generally declared as inerts, and for this reason they are not tested in long-term regulatory experiments. It is thus very surprising that they amplify up to 1000 times the toxicity of their APs [Active Principles] in 100% of the cases where they are indicated to be present by the manufacturer. ” *R. Mesnage et al. Bio. Med Research International 2014; Article ID: 179691.

Some Biomarkers for Autism • • • Disrupted gut bacteria; inflammatory bowel Low serum

Some Biomarkers for Autism • • • Disrupted gut bacteria; inflammatory bowel Low serum sulfate Methionine deficiency Serotonin and melatonin deficiency Defective aromatase Zinc and iron deficiency Urinary p-cresol Mitochondrial disorder Glutamate toxicity in the brain

Some Biomarkers for Autism • • • Disrupted gut bacteria; inflammatory bowel Low serum

Some Biomarkers for Autism • • • Disrupted gut bacteria; inflammatory bowel Low serum sulfate Methionine deficiency These can all be explained as potential Serotonin and melatonin deficiency effects of glyphosate on biological systems Defective aromatase Zinc and iron deficiency Urinary p-cresol Mitochondrial disorder Glutamate toxicity in the brain

Dementia and Autism Have Much in Common Plot kindly provided by Nancy Swanson

Dementia and Autism Have Much in Common Plot kindly provided by Nancy Swanson

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Roundup Safety Claims Disputed* “It is commonly believed that Roundup is among the safest

Roundup Safety Claims Disputed* “It is commonly believed that Roundup is among the safest pesticides. … Despite its reputation, Roundup was by far the most toxic among the herbicides and insecticides tested. This inconsistency between scientific fact and industrial claim may be attributed to huge economic interests, which have been found to falsify health risk assessments and delay health policy decisions. ” *R. Mesnage et al. , Biomed Research International, Volume 2014 (2014), Article ID 179691

Glyphosate Test Report: Findings in American Mother's Breast milk, urine and water* • Moms

Glyphosate Test Report: Findings in American Mother's Breast milk, urine and water* • Moms Across America initiative! • Breast milk levels ranging from 76 ug/l to 166 ug/l are 760 to 1600 times higher than the European Drinking Water Directive allows • Urine testing shows glyphosate levels over 10 times higher than in Europe • Monsanto is wrong regarding bioaccumulation *Posted on Apr 6 2014 - 4: 19 am by Sustainable Pulse

“Another claim of Monsanto's has been that residue levels of up to 5. 6

“Another claim of Monsanto's has been that residue levels of up to 5. 6 mg/kg in GM-soy represent ". . . extreme levels, and far higher than those typically found" (Monsanto 1999). ” 5. 6 *Figure 1, T. Bohn et al. Food Chemistry 153, 15 June 2014, 207 -215. www. greenmedinfo. com/blog/how-extreme-levels-roundup-food-became-industry-normal

Soy Formula Linked to Seizures in Autism* "There was a 2. 6 -fold higher

Soy Formula Linked to Seizures in Autism* "There was a 2. 6 -fold higher rate of febrile seizures, a 2. 1 -fold higher rate of epilepsy comorbidity and a 4 -fold higher rate of simple partial seizures in the autistic children fed soybased formula" *CJ Westmark, PLOSOne March 12, 2014, DOI: 10. 1371/journal. pone. 0080488.

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Two Papers

Two Papers

The First Paper • This paper used the US CDC VAERS database to link

The First Paper • This paper used the US CDC VAERS database to link together preeclampsia, autism and pernicious anemia • Pernicious anemia is due to cobalamin (B 12) deficiency • Preeclampsia is a strong risk factor for autism • The symptoms in adverse reactions linked to anemia recapitulate preeclampsia

The First Paper • This paper used the US CDC VAERS database to link

The First Paper • This paper used the US CDC VAERS database to link together preeclampsia, autism and pernicious anemia Glyphosate chelates cobalt • Pernicious anemia is due to cobalamin (B 12) which prevents gut bacteria from deficiencyproducing cobalamin • Preeclampsia is a strong risk factor for autism • The symptoms in adverse reactions linked to anemia recapitulate preeclampsia

Figure from Our First Paper* Glyphosate *S. Seneff et al. , Entropy 2012, 14,

Figure from Our First Paper* Glyphosate *S. Seneff et al. , Entropy 2012, 14, 2265 -2290.

Figure from Our Second Paper* *S. Seneff et al. Entropy 2013, 15(1), 372 -406.

Figure from Our Second Paper* *S. Seneff et al. Entropy 2013, 15(1), 372 -406.

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate increases glutamate Glyphosate activates NMDA receptors Glyphosate depletes serotonin *S. Seneff et al. Entropy 2013, 15(1), 372 -406.

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Autism, Glyphosate, Vaccine Reactions* Glyphosate application to corn and soy, US Children with Autism,

Autism, Glyphosate, Vaccine Reactions* Glyphosate application to corn and soy, US Children with Autism, US # Adverse Reactions in VAERS *Collaboration with Nancy Swanson MIT Computer Science and Artificial Intelligence Laboratory

Autism, Glyphosate, Vaccine Reactions* Glyphosate application to corn and soy, US Glyphosate makes the

Autism, Glyphosate, Vaccine Reactions* Glyphosate application to corn and soy, US Glyphosate makes the aluminum (and Children with Autism, US mercury? ) in vaccines much more toxic # Adverse Reactions in VAERS *Collaboration with Nancy Swanson MIT Computer Science and Artificial Intelligence Laboratory

Glyphosate enhances aluminum toxicity Glyphosate interferes with acetaminophen metabolism

Glyphosate enhances aluminum toxicity Glyphosate interferes with acetaminophen metabolism

Aluminum Glyphosate* Six different ways two glyphosate molecules can chelate aluminum Aluminum citrate** ALUMINA

Aluminum Glyphosate* Six different ways two glyphosate molecules can chelate aluminum Aluminum citrate** ALUMINA aluminum *M. Purgel et al. , Journal of Inorganic Biochemistry 103 (2009) 1426– 1438 ** P. Sianina et al. , Clin. Chem. 32/3, 539 -541, 1986.

Aluminum & Mercury Autism & PDD & Anxiety VAERS database Formula: Al + 1.

Aluminum & Mercury Autism & PDD & Anxiety VAERS database Formula: Al + 1. 5 x (Al w/ Hg) + 2. 0 x Hg

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Glyphosate chelates many metal cations: I suspect many adverse health effects from chelation of

Glyphosate chelates many metal cations: I suspect many adverse health effects from chelation of aluminum, arsenic, manganese, and cobalt

Glyphosate chelates many metal cations: I suspect many adverse health effects from chelation of

Glyphosate chelates many metal cations: I suspect many adverse health effects from chelation of aluminum, arsenic, manganese, and cobalt

Sri Lanka is the first Country to Ban Glyphosate arsenic This problem did not

Sri Lanka is the first Country to Ban Glyphosate arsenic This problem did not exist in Sri Lanka prior to the 1990 s.

Acute Kidney Disease Death Rate Plotted Against Glyphosate and GMOs* *Plot prepared by Nancy

Acute Kidney Disease Death Rate Plotted Against Glyphosate and GMOs* *Plot prepared by Nancy Swanson from available data online

Acute Kidney Disease Death Rate Plotted Against Glyphosate and GMOs* Young male agricultural works

Acute Kidney Disease Death Rate Plotted Against Glyphosate and GMOs* Young male agricultural works in sugarcane fields desiccated with glyphosate are dying from kidney disease *Plot prepared by Nancy Swanson from available data online

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Manganese!

Manganese!

“The mechanism by which glyphosate disrupts the EPSPS enzyme in plants and microorganism is

“The mechanism by which glyphosate disrupts the EPSPS enzyme in plants and microorganism is by chelating the manganese metal co-factor of this enzyme. In other words it steals the ‘ignition key’ of the enzyme. ” Dr. Arden Andersen, D. O. , Food Plague Primer: Glyphosate and Genetically Engineered Crops

“Fundamentally the herbicidal effect of glyphosate is ultimately due to soil pathogens gaining access

“Fundamentally the herbicidal effect of glyphosate is ultimately due to soil pathogens gaining access to the “weed” thanks to glyphosate’s weakening of the plant and killing of beneficial microbes by the chelation of manganese and other trace elements. ” Dr. Arden Andersen, D. O. , Food Plague Primer: Glyphosate and Genetically Engineered Crops

“Fundamentally the herbicidal effect of glyphosate is ultimately due to soil pathogens gaining access

“Fundamentally the herbicidal effect of glyphosate is ultimately due to soil pathogens gaining access This is analogous to glyphosate’s effect on to the “weed” thanks to glyphosate’s weakening of gut bacteria: killing the beneficial bacteria the plant and killing of beneficial microbes by the and allowing the pathogens to overgrow chelation of manganese and other trace elements. ” Dr. Arden Andersen, D. O. , Food Plague Primer: Glyphosate and Genetically Engineered Crops

Glyphosate Depletes Iron, Manganese and Zinc in Plants* *D Huber, What About Glyphosate-Induced Manganese

Glyphosate Depletes Iron, Manganese and Zinc in Plants* *D Huber, What About Glyphosate-Induced Manganese Deficiency? Fluid Journal, 20 -22.

Severe Deficiency in Serum Manganese and Cobalt in Cows* Eight different farms: all cows

Severe Deficiency in Serum Manganese and Cobalt in Cows* Eight different farms: all cows tested had glyphosate in the urine *M. Krüger et al. , J Environ Anal Toxicol 2013, 3: 5

Severe Deficiency in Serum Manganese and Cobalt in Cows* cobalamin deficiency ? ? ?

Severe Deficiency in Serum Manganese and Cobalt in Cows* cobalamin deficiency ? ? ? Eight different farms: all cows tested had glyphosate in the urine *M. Krüger et al. , J Environ Anal Toxicol 2013, 3: 5

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Glyphosate Kills Beneficial Bacteria* • Examined effect of glyphosate and Roundup on three food

Glyphosate Kills Beneficial Bacteria* • Examined effect of glyphosate and Roundup on three food microorganisms widely used as starters in dairy technologies – Two are species of Lactobacillus • Roundup is always more potent than glyphosate, and in all cases, toxic from levels 10– 100 times below the lowest agricultural uses (10, 000 ppm). • Unpredictable consequences of Roundup on soil microorganisms have to be considered *E Clair et al. Curr Microbiol (2012) 64: 486– 491

Lactobacillus Depends on Manganese!* • Many lactic acid bacteria contain very high intracellular manganese

Lactobacillus Depends on Manganese!* • Many lactic acid bacteria contain very high intracellular manganese levels – Scavenges toxic oxygen species, particularly superoxide • Manganese deprivation suppresses growth * FS Archibald and M-N Duong. Journal of Bacteriology Apr 1084, 1 -8.

Lactobacillus Depends on Manganese!* • Many lactic acid bacteria contain very high intracellular manganese

Lactobacillus Depends on Manganese!* • Many lactic acid bacteria contain very high intracellular manganese levels – Scavenges toxic oxygen species, Lactobacillus levels are low in the gut particularly superoxide in association with autism • Manganese deprivation suppresses growth * FS Archibald and M-N Duong. Journal of Bacteriology Apr 1084, 1 -8.

Lactobacillus Alleviate Anxiety* • Patients suffered from chronic fatigue syndrome and associated anxiety •

Lactobacillus Alleviate Anxiety* • Patients suffered from chronic fatigue syndrome and associated anxiety • Patients were treated with probiotic strain of Lactobacillus (control group got a placebo) • Significant rise in both Latobacillus and Bifidobacteria in gut • Significant decrease in anxiety symptoms (p = 0. 01) • Supports concept of gut-brain axis (communicate with brain via vagal nerve) *R Av et al. Gut Pathog. 2009 Mar 19; 1(1): 6. doi: 10. 1186/1757 -4749 -1 -6.

Lactobacillus Alleviate Anxiety* • Patients suffered from chronic fatigue syndrome and associated anxiety •

Lactobacillus Alleviate Anxiety* • Patients suffered from chronic fatigue syndrome and associated anxiety • Patients were treated with probiotic strain of Lactobacillus (control group got a placebo) Increased anxiety is a comorbidity of autism • Significant rise in both Latobacillus and Bifidobacteria in gut • Significant decrease in anxiety symptoms (p = 0. 01) • Supports concept of gut-brain axis (communicate with brain via vagal nerve) *R Av et al. Gut Pathog. 2009 Mar 19; 1(1): 6. doi: 10. 1186/1757 -4749 -1 -6.

Anxiety and Autism* • • • Specific Phobia: 30% Obsessive-Compulsive Disorder: 17% Social Anxiety

Anxiety and Autism* • • • Specific Phobia: 30% Obsessive-Compulsive Disorder: 17% Social Anxiety Disorder/Agoraphobia: 17% Generalized Anxiety Disorder: 15% Separation Anxiety Disorder: 9 % Panic Disorder: 2% *Van Steensel, F. J. A. , Bogels, S. M. , & Perrin, S. (2011). Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clinical Child and Family Psychology Review, 14, 302 -317.

Glyphosate Application on Corn and Soy Plotted against Anxiety, Panic Disorder and Phobias* *Plots

Glyphosate Application on Corn and Soy Plotted against Anxiety, Panic Disorder and Phobias* *Plots provided by Dr. Nancy Swanson

Bacteria Incorporate Cobalt and Iron into Cobalamin and Heme Cobalamin Heme Iron

Bacteria Incorporate Cobalt and Iron into Cobalamin and Heme Cobalamin Heme Iron

Bacteria Incorporate Cobalt and Iron into Cobalamin and Heme Glyphosate chelates cobalt and iron

Bacteria Incorporate Cobalt and Iron into Cobalamin and Heme Glyphosate chelates cobalt and iron and prevents bacteria from producing these important molecules Cobalamin Heme Iron

The First Paper • This paper used the US CDC VAERS database to link

The First Paper • This paper used the US CDC VAERS database to link together preeclampsia, autism and pernicious anemia • Pernicious anemia is due to cobalamin (B 12) deficiency • Preeclampsia is a strong risk factor for autism • The symptoms in adverse reactions linked to anemia recapitulate preeclampsia

The First Paper • This paper used the US CDC VAERS database to link

The First Paper • This paper used the US CDC VAERS database to link together preeclampsia, autism and pernicious anemia • Pernicious anemia is due to cobalamin (B 12) deficiency • Preeclampsia is a strong risk factor for autism • The symptoms in adverse reactions linked to anemia recapitulate preeclampsia

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Glyphosate and Glutamate* • Acute exposure activates NMDA receptors and voltage-dependent calcium channels –

Glyphosate and Glutamate* • Acute exposure activates NMDA receptors and voltage-dependent calcium channels – Oxidative stress and neural cell death – Increased glutamate released into the synaptic cleft excessive extracellular glutamate levels – Decreased glutathione content – Increased peroxidation of lipids (fats) • Chronic exposure: – Decreased glutamate uptake and metabolism – Induced calcium uptake – Induced oxidative stress *http: //www. greenmedinfo. com/blog/roundup-weedkiller-brain-damaging-neurotoxin

Glutamine Synthesis Depends on Manganese! Glutamine synthetase glutamate water ammonium glutamine Ammonium and glutamate

Glutamine Synthesis Depends on Manganese! Glutamine synthetase glutamate water ammonium glutamine Ammonium and glutamate toxicity in the brain can arise because of insufficient manganese

Glutamate and GABA* *NM Rowley et al. Neurochemistry International 61 (2012) 546– 558.

Glutamate and GABA* *NM Rowley et al. Neurochemistry International 61 (2012) 546– 558.

Glutamate and GABA* Glutamate and ammonia both build up to toxic levels because of

Glutamate and GABA* Glutamate and ammonia both build up to toxic levels because of manganese deficiency *NM Rowley et al. Neurochemistry International 61 (2012) 546– 558.

“Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism”* *C. Shimmura

“Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism”* *C. Shimmura et al. PLo. Sone October 2011 6(1): e 25340

Journal of Personal Science: One Child’s Autism Eliminated by Removal of Glutamate From Her

Journal of Personal Science: One Child’s Autism Eliminated by Removal of Glutamate From Her Diet* By Katherine Reid First Round: – – Kale, cucumber, cilantro, nuts, seeds, fruits Magnesium B-complex, vitamin D 3, omega 3 fats (EPA, DHA) Probiotics Gluten free and casein free (no wheat, no milk) Child improved significantly but still had autistic behaviors Second Round: – ADD: ELIMINATE FREE GLUTAMATE Child lost the "autism" label! *blog. sethroberts. net/2013/05/17/journal-of-personal-scienceone-childs-autism-eliminated-by-removal-of-glutamate-from-her-diet

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate increases glutamate Glyphosate activates NMDA receptors Glyphosate depletes serotonin *S. Seneff et al. Entropy 2013, 15(1), 372 -406.

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate

Figure from Our Second Paper* Glyphosate depletes glutathione and methionine Glyphosate increases ammonia Glyphosate increases glutamate Glyphosate activates NMDA receptors Glyphosate depletes serotonin *S. Seneff et al. Entropy 2013, 15(1), 372 -406.

Glyphosate suppresses tryptophan Glyphosate suppresses aromatase which Glyphosate suppresses vitamin D activation in the

Glyphosate suppresses tryptophan Glyphosate suppresses aromatase which Glyphosate suppresses vitamin D activation in the liver synthesis by plants and gut bacteria converts testosterone to estrogen • Autism is associated with low activated vitamin D and low brain serotonin – Vitamin D activates serotonin receptors in the brain • Estrogen rescues females by boosting serotonin levels in brain • Recommendation is supplements in both vitamin D and tryptophan (precursor to serotonin)

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Autism and Mitochondrial Disorder* “Five of 11 patients studied were classified with definite mitochondrial

Autism and Mitochondrial Disorder* “Five of 11 patients studied were classified with definite mitochondrial respiratory chain disorder, suggesting that this might be one of the most common disorders associated with autism” Manganese superoxide dismutase plays a critical role in protecting mitochondria from oxidative damage *G Oliveira et al. Developmental Medicine & Child Neurology 47(3), 185 -189, 2005.

Detoxification of Superoxide (O 2 -) GLUTATHIONE SELENIUM MANGANESE Glyphosate disrupts all of these!

Detoxification of Superoxide (O 2 -) GLUTATHIONE SELENIUM MANGANESE Glyphosate disrupts all of these! IRON

Citric Acid Cycle in Mitochondria aconitase *PR Gardner. Methods in Enzymology 349: 9– 23.

Citric Acid Cycle in Mitochondria aconitase *PR Gardner. Methods in Enzymology 349: 9– 23.

Citric Acid Cycle in Mitochondria aconitase The iron sulfur cluster in aconitase is highly

Citric Acid Cycle in Mitochondria aconitase The iron sulfur cluster in aconitase is highly sensitive to oxidation by superoxide* *PR Gardner. Methods in Enzymology 349: 9– 23.

Aconitase Dysfunction and Brain Inflammation in Autism* • Frozen samples of post-mortem tissues from

Aconitase Dysfunction and Brain Inflammation in Autism* • Frozen samples of post-mortem tissues from cerebellum and temporal cortex of autism patients compared with controls. • Compared to controls: – Aconitase activity was significantly reduced in the cerebellum and correlated with low glutathione levels – Biomorkers of inflammation were increased *S. Rose et al. Transl Psychiatry (2012) 2: e 134.

Aconitase & Glutathione in Cerebellum in Autism* * S Rose et al. Transl Psychiatry

Aconitase & Glutathione in Cerebellum in Autism* * S Rose et al. Transl Psychiatry (2012) 2: e 134.

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Maternal Low Thyroid and Autism* “Severe maternal hypothyroxinemia early in gestation increased the likelihood

Maternal Low Thyroid and Autism* “Severe maternal hypothyroxinemia early in gestation increased the likelihood of having an autistic child by almost 4 -fold. ” Thyroid hormone is derived from tyrosine, one of the three aromatic amino acids produced via the shikimate pathway *http: //www. medscape. com/viewarticle/809718

Dopamine and Thyroid Hormone* • Like thyroid hormone, dopamine is derived from the aromatic

Dopamine and Thyroid Hormone* • Like thyroid hormone, dopamine is derived from the aromatic amino acid tyrosine • Dopamine inhibits thyroid stimulating hormone – Corollary: insufficient dopamine leads to overactive thyroid burnout • Thyroid hormone promotes synaptogenesis, synaptic vesicle and receptor recycling, neurotransmitter reuptake, and growth factor receptor signaling *OP Soldin and M Aschner. Neurotoxicology 2007 September; 28(5): 951– 956

Glyphosate and Thyroid Cancer* *Graph kindly provided by Nancy Swanson

Glyphosate and Thyroid Cancer* *Graph kindly provided by Nancy Swanson

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Glyphosate and Bone Development* • Dams treated with glyphosate in water from days 6

Glyphosate and Bone Development* • Dams treated with glyphosate in water from days 6 to 15 of their pregnancy • Effects on pups: – Lack of development of the ossification centers of the terminal phalanges (bones in fingers and toes) – Larger fontanelles ("soft spot") and incomplete development of skull bones – Absence of important bones or parts of bones, shortenings, bendings, asymmetry, fusions or clefts. – Surfactant polyoxyethyleneamine increased glyphosate's toxicity *E. Dallegrave et al. Toxicology Letters 142 (2003) 45 -52.

Manganese and Bones* “The multiple cellular effects of Mn deficiency include: decreased bone resorption,

Manganese and Bones* “The multiple cellular effects of Mn deficiency include: decreased bone resorption, production of labile bone, and decreased synthesis of organic matrix. The serum level of Mn in a group of osteoporotic postmenopausal women was significantly lower than age-matched controls. ” *L. Strause and P. Saltman. Role of Manganese in Bone Metabolism. Chapter 5, pp 46– 55 in Nutritional Bioavailability of Manganese.

Osteoblasts build “Ground Substance” • Ground substance is made of chondroitin sulfate and osteocalcin

Osteoblasts build “Ground Substance” • Ground substance is made of chondroitin sulfate and osteocalcin – collagen is layered over this • Poor mineralization results from impaired chondroitin sulfate synthesis Osteoblasts in bone Childhood osteoarthritis and osteomalacia are an epidemic in the US today

Chondroitin Sulfate Synthesis in Cartilage depends on Manganese* • Two critical enzymes are manganese

Chondroitin Sulfate Synthesis in Cartilage depends on Manganese* • Two critical enzymes are manganese dependent: – Polymerase enzyme forms the polysaccharide – Galactotransferase incorporates galactose that links the polysaccharide to the protein associated with it. *RM Leach et al. Archives of Biochemistry and Biophysics 133(1), 1969, 22 -28.

Perineuronal Nets* • Perineuronal nets (PNs) formed from chondroitin sulfate attached to hyaluronan, modulate

Perineuronal Nets* • Perineuronal nets (PNs) formed from chondroitin sulfate attached to hyaluronan, modulate GABAergic inhibitory signaling • Removal of PNs increased the excitability of interneurons in cultures • They provide an environment rich in anions (negative charge) *G. Bruckner et al. Glia 8(3), 183 -200, 1993.

Perineuronal Nets* • Perineuronal nets (PNs) formed from chondroitin sulfate attached to hyaluronan, modulate

Perineuronal Nets* • Perineuronal nets (PNs) formed from chondroitin sulfate attached to hyaluronan, modulate GABAergic inhibitory signaling Might manganese deficiency lead to • Removal of PNs increased the impaired synthesis of perineuronal excitability of interneurons nets and increased neuronal in cultures excitability leading to cell death? ? • They provide an environment rich in anions (negative charge) *G. Bruckner et al. Glia 8(3), 183 -200, 1993.

Coral Die-Off & Chondroitin Sulfate* • Large amounts of chondroitin sulfate are adsorbed onto

Coral Die-Off & Chondroitin Sulfate* • Large amounts of chondroitin sulfate are adsorbed onto coral • Sulfate groups are of paramount importance to the adsorption process • Adsorption rate is a direct function of the amount of negative charge *N. Volpi. Biomaterials 2002 Jul; 23(14): 3015 -22.

“Disease Causes Starfish to Lose Arms, Dissolve into White Blobs of Goo” * •

“Disease Causes Starfish to Lose Arms, Dissolve into White Blobs of Goo” * • Glyphosate is used to kill seagrass in oyster beds • "Glyphosate and diuron are among the most frequently detected herbicides in oyster production areas"** • Starfish eat oysters *http: //natureworldnews. com/articles/4749/20131104/ disease-causes-starfish-lose-arms-dissolve-white-blobs-goo-video. htm **F. Akcha et al. Aquatic Toxicology. 106 -107 (pp 104 -113), 2012

Recapitulation • Glyphosate chelates manganese • Manganese deficiency leads to: – Disrupted gut bacteria

Recapitulation • Glyphosate chelates manganese • Manganese deficiency leads to: – Disrupted gut bacteria anxiety – Tyrosine depletion thyroid disease – Glutamate and ammonium toxicity in the brain as well as glutamine deficiency – Mitochondrial damage – Impaired bone development and osteoporosis – Impaired development of perineuronal nets • Many of these pathologies are associated with autism

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My

Outline • • • Autism and glyphosate: Introduction Glyphosate is TOXIC to humans My earlier papers reexamined Glyphosate and aluminum Glyphosate and arsenic Glyphosate and manganese – Lactobacillus and anxiety – Glutamate and ammonia – Mitochondrial disorder – Thyroid hormone – Impaired bone development • Recommendations and Summary

Foods High in Sulfur

Foods High in Sulfur

Foods High in Manganese

Foods High in Manganese

Go Organic!

Go Organic!

Summary • Contrary to popular belief, glyphosate is toxic to humans and is likely

Summary • Contrary to popular belief, glyphosate is toxic to humans and is likely the number one factor in the autism epidemic • Glyphosate’s chelation of rare minerals is a core component of its toxicity – Disrupted gut bacteria leads to multiple problems – Aluminum and manganese pathology can account for many aspects of autism • Dementia may well be the same story • Autism may be treatable through organic diet enriched in sulfur and manganese